The following is an excerpt from this week's CQ Researcher issue on "Breast Cancer" by Barbara Mantel, April 2, 2010~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

There is no single cause of breast cancer. Yet understanding the etiology of this complex disease is essential to understanding how to prevent it. While 5 to 10 percent of breast cancer cases are thought to be hereditary, the majority of women who develop the disease will never know why.

Scientists have identified certain risk factors, like early menstruation and late menopause, alcohol consumption and obesity, but “most of these risk factors account for very small increases or decreases in a woman's chances of developing breast cancer,” according to the National Breast Cancer Coalition. [Footnote 28]

Environmental chemicals may play a role, say some researchers, by damaging DNA, by mimicking hormones that signal tumor cells to grow or by altering mammary gland development early in life. They say the size of the dose may not be what matters most but how early in life and for how long the exposure occurs and to whom; some women may be more susceptible than others. “Breast cancer rates increased enormously over the decades since World War II at the same time that we have had increasing exposure to a wide variety of chemicals and radiation in the environment,” says Janet Gray, director of the program in science, technology and society at Vassar College in Poughkeepsie, N.Y., who wrote an extensive review of the research on breast cancer and the environment for the Breast Cancer Fund, an advocacy group in San Francisco, Calif.

But correlation does not prove a link. For that, scientists turn to animal and human studies. One team of researchers reviewed hundreds of animal studies and found that 216 chemicals have been shown to cause mammary gland tumors, mostly through DNA mutations. There could be many others, since only a small fraction of the more than 80,000 chemicals used in the United States today have been tested in animals for carcinogenic potential. [Footnote 29]

“The laboratory evidence is very strong that there are environmental chemicals that affect biological processes linked to breast cancer,” says Julia G. Brody, who participated in the review of chemicals and is the executive director of the Silent Spring Institute in Newton, Mass., which researches the environment and women's health. The chemicals include benzene, found in gasoline; polycyclic aromatic hydrocarbons, found in vehicle exhaust, air pollution, tobacco smoke and charred foods; methylene chloride, a common solvent in paint strippers and glues; and some pharmaceuticals, like furosemide, a diuretic, and griseofulvin, an anti-fungal. [Footnote 30]

Most of the 216 chemicals also caused tumors in multiple organs, not just mammary tissue, and in multiple species of animals. “These characteristics are generally believed to indicate likely carcinogenicity in humans,” Brody's team reported. [Footnote 31]

A growing number of animal studies also implicate endocrine-disrupting compounds (EDCs) — found in certain plastics, pesticides, flame retardants and personal care products — which mimic or block hormones. “There are literally hundreds of studies demonstrating that low doses of endocrine disruptors in early development have profound effects on mammary tissue, breast development and incidence of breast cancer, especially in a variety of rodent models,” says Gray. [Footnote 32]

But extrapolating from animal studies to the human experience is tricky. “We're on very thin ice inferring from animal models that there's a high probability that a chemical is a carcinogen in humans,” says David Hunter, a professor of epidemiology at Harvard University in Cambridge, Mass. “There is a relatively low correlation between exposures that cause cancer in animals and those exposures causing cancer in humans,” says Hunter. “And if there is a relationship, it's a different type of cancer in the human compared to the animal.”

The gold standard would be human studies, but there haven't been many, and most that have been done have not found a link. Perhaps that's because human studies have mostly measured levels of a single chemical in adult women, while the critical period of exposure might be puberty, or early childhood, or even in utero. In addition, it might be exposure to a mix of chemicals that is important.

But it is extremely difficult to study early exposure to multiple chemicals. Most people don't know what chemicals they are exposed to now, let alone decades ago. And when interviewing women with breast cancer, “How do you know the diagnosis itself isn't influencing their recall of events?” asks James Lacey, a cancer epidemiologist at City of Hope, a comprehensive cancer center in Duarte, Calif. “People want to put a narrative to their experiences,” he says. Researchers also may not be able to find an unexposed control group, since many chemicals are pervasive. And finally, chemicals may increase breast cancer risk only for women with certain genetic mutations.

Instead, some researchers have combed through state environmental data and medical records looking for reliable information. One group found blood samples taken from young women at the time they gave birth, measured their levels of the pesticide DDT, and then followed the women for two decades. Early exposure to DDT was associated with a fivefold increase in risk of developing breast cancer before age 50. [Footnote 33] DDT, though banned in 1972, continues to linger in the environment.

“That is an important study, and it provides the kind of evidence that is very difficult to get,” says Brody.

Four human studies show higher breast cancer risk from exposure to polychlorinated bipheyls (PCBs) in women with a gene mutation that affects how they metabolize these now banned chemicals that were once used in electrical equipment, but still linger.

But Hunter cautions that no single epidemiological study is definitive. “We only accept something as likely to be causal if the majority of studies point in the same direction,” he says. Brody also calls the number of human studies sparse and says there are “huge knowledge gaps.”

Experts say more chemicals must be tested — both in the lab and in animals and in forward-looking human studies — not dependent on memory. For instance, the federal National Children's Study will examine the effects of environmental influences on the health and development of 100,000 children in the United States, following them from before birth until age 21. [Footnote 34]

“However, that doesn't help us right now,” says Gray. That's why she and Brody both advocate relying on the animal data to propel action in the short term. “I don't think most families want to take unnecessary risks with their daughters,” says Brody. A progressive policy, she says, would acknowledge that we know enough now to start reducing those exposures.

For Michael Thun, emeritus vice president of epidemiology and surveillance at the American Cancer Society, it's not so clear. “The precautionary principle says that if you have some evidence you should take action — you don't need conclusive evidence — but the question that remains unresolved is where do you draw the line?” says Thun.

Brody says the U.S. should look to Europe and Canada for a model of how to implement the precautionary principle. These countries have developed systematic programs for assessing the health consequences of synthetic chemicals — both old and new — as a prerequisite for use. [Footnote 35]

Is mammography oversold?

Should “stage zero” cancer be watched and not treated?

Do chemicals in the environment cause breast cancer?

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